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Effects of TGF-β Overexpression via rAAV Gene Transfer on the Early Repair Processes in an Osteochondral Defect Model in Minipigs.
- Source :
-
American Journal of Sports Medicine . Jul2018, Vol. 46 Issue 8, p1987-1996. 10p. - Publication Year :
- 2018
-
Abstract
- Background: Application of the chondrogenic transforming growth factor beta (TGF-β) is an attractive approach to enhance the intrinsic biological activities in damaged articular cartilage, especially when using direct gene transfer strategies based on the clinically relevant recombinant adeno-associated viral (rAAV) vectors. Purpose: To evaluate the ability of an rAAV–TGF-β construct to modulate the early repair processes in sites of focal cartilage injury in minipigs in vivo relative to control (reporter lacZ gene) vector treatment. Study Design: Controlled laboratory study. Methods: Direct administration of the candidate rAAV–human TGF-β (hTGF-β) vector was performed in osteochondral defects created in the knee joint of adult minipigs for macroscopic, histological, immunohistochemical, histomorphometric, and micro–computed tomography analyses after 4 weeks relative to control (rAAV-lacZ) gene transfer. Results: Successful overexpression of TGF-β via rAAV at this time point and in the conditions applied here triggered the cellular and metabolic activities within the lesions relative to lacZ gene transfer but, at the same time, led to a noticeable production of type I and X collagen without further buildup on the subchondral bone. Conclusion: Gene therapy via direct, local rAAV–hTGF-β injection stimulates the early reparative activities in focal cartilage lesions in vivo. Clinical Relevance: Local delivery of therapeutic (TGF-β) rAAV vectors in focal defects may provide new, off-the-shelf treatments for cartilage repair in patients in the near future. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ANALYSIS of variance
*ANIMAL experimentation
*COMPUTED tomography
*CONFIDENCE intervals
*GENE expression
*GENE therapy
*HISTOLOGICAL techniques
*IMMUNOHISTOCHEMISTRY
*PROBABILITY theory
*STAINS & staining (Microscopy)
*STATISTICS
*SWINE
*TRANSFORMING growth factors-beta
*ARTICULAR cartilage injuries
*STATISTICAL power analysis
*DATA analysis
*DATA analysis software
*DESCRIPTIVE statistics
*IN vivo studies
Subjects
Details
- Language :
- English
- ISSN :
- 03635465
- Volume :
- 46
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- American Journal of Sports Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 130695678
- Full Text :
- https://doi.org/10.1177/0363546518773709